Bromoacetonitrile → N-((1-(cyanomethyl)piperidin-4-yl)methyl)-3,5-bis(trifluoromethyl)benzamide

HRID 388766Notes

Reaction equation

[NH:1]1[CH2:6][CH2:5][CH:4]([CH2:7][NH:8][C:9](=[O:24])[C:10]2[CH:15]=[C:14]([C:16]([F:19])([F:18])[F:17])[CH:13]=[C:12]([C:20]([F:23])([F:22])[F:21])[CH:11]=2)[CH2:3][CH2:2]1.[CH3:25][CH2:26][N:27](C(C)C)C(C)C.BrCC#N>CC#N>[C:26]([CH2:25][N:1]1[CH2:6][CH2:5][CH:4]([CH2:7][NH:8][C:9](=[O:24])[C:10]2[CH:11]=[C:12]([C:20]([F:21])([F:22])[F:23])[CH:13]=[C:14]([C:16]([F:18])([F:19])[F:17])[CH:15]=2)[CH2:3][CH2:2]1)#[N:27]

Participants

Conditions

Temperature: 50 °C

Procedure

N-(piperidin-4-ylmethyl)-3,5-bis(trifluoromethyl)benzamide (3.54 g, 10.0 mmol) was dissolved in CH3CN (100 mL). DIPEA (1.94 g, 15.0 mmol) and bromoacetonitrile (1.32 g, 11.0 mmol) were added. The reaction mixture was heated at 50° C. overnight. The solvent was removed in vacuo. Saturated NaHCO3 (40 mL) was added and the mixture was extracted with CH2Cl2 (4×30 mL). The combined organic solution was dried over anhydrous Na2SO4 and passed through a silica gel plug. The desired compound was eluted off with EtOAc. The product was further purified by crystallization from EtOAc/petroleum ether as a white solid (3.62 g, 92%).

Workup

customThe solvent was removed in vacuo
additionSaturated NaHCO3 (40 mL) was added
extractionthe mixture was extracted with CH2Cl2 (4×30 mL)
dry with materialThe combined organic solution was dried over anhydrous Na2SO4
washThe desired compound was eluted off with EtOAc
customThe product was further purified by crystallization from EtOAc/petroleum ether as a white solid (3.62 g, 92%)

Sources & evidence

ORD record: ord-8e5b7e5f5da74fa8bfdeed53289e80a2
Source dataset: uspto-grants-2013_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08377968B2

Reaction notes

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